Intravenous beta(2)-agonists versus intravenous aminophylline for acute asthma

Cochrane Database Syst Rev. 2012 Dec 12;12:CD010256. doi: 10.1002/14651858.CD010256.


Background: Inhaled beta(2)-agonist therapy is central to the management of acute asthma. For rapid bronchodilation in severe cases, penetration of inhaled drug to the affected small conducting airway may be impeded, and the intravenous (IV) rather than inhaled administration of bronchodilators may provide an earlier response. IV beta(2)-agonist agents and IV aminophylline may also be considered as additional interventions in this setting and this review compares IV beta-agonist agents and IV aminophylline in the treatment of people with acute asthma.

Objectives: To compare the benefit of IV beta(2)-agonists versus IV aminophylline for acute asthma treated in the emergency department and in patients admitted to hospital with acute severe asthma.

Search methods: Randomised controlled trials (RCTs) were identified using the Cochrane Airways Group Register, which is compiled from systematic searches of bibliographic databases as well as handsearching of respiratory journals and conference abstracts. The latest search was run in September 2012. We searched bibliographies from included studies and known reviews were also searched. Primary authors and content experts were contacted to identify eligible studies.

Selection criteria: We included RCTs of patients who presented to the emergency department with acute asthma, and patients admitted to hospital with acute severe asthma, and were treated with IV beta(2)-agonists versus IV aminophylline. Two review authors independently selected potentially relevant articles and selected articles for inclusion. Methodological quality was independently assessed using two scoring systems and two review authors.

Data collection and analysis: Data were extracted independently by two review authors. Missing data were obtained from authors or calculated from data present in the papers. Trials were combined using a random-effects model for odds ratios (OR) or mean differences (MD) and reported with 95% confidence intervals (95% CI).

Main results: Eleven studies met our inclusion criteria and in total they included 350 patients. However, opportunities to combine these studies in meta-analyses were limited by the variations in the range of outcomes reported in the trials.Length of stayTwo studies reported length of stay. They were both paediatric trials (with one in paediatric intensive care unit), and there was no significant difference between the two groups (MD 23.19 hours; 95% CI -2.40 to 48.77 hours; 2 studies; N = 73). Individual separate MD analyses for the two studies also indicated no significant difference between the aminophylline and beta(2)-agonist on this outcome. However, this finding should be interpreted with caution owing to the small number of trials and participants the analysis.Pulmonary functionThere were no significant differences in the sequential or summative pulmonary function demonstrated across the studies.Heart rateData for serial heart rates were reported in three studies at various points from 15 to 60 minutes and in each case there were no significant differences between people in the IV aminophylline or beta(2)-agonist groups. The difference between the two groups with respect to final heart rate was statistically significant (MD 10.00; 95% CI 0.99 to 19.01), although these data are from a single, small study and should be interpreted with caution.Adverse effectsThe analyses for giddiness (OR 59.22; 95% CI 2.80 to 1253.05; 1 study; N = 30), nausea/vomiting (where reported as a combined outcome) (OR 14.18; 95% CI 1.62 to 124.52; 2 studies; N = 96) and nausea (OR 6.53; 95% CI 1.60 to 26.72; 2 studies; N = 49) all significantly favoured beta(2)-agonists. In view of the very small number of studies and number of patients contributing to these analyses these results should be interpreted with caution. A closely related review considering the possible benefits of adding IV aminophylline to beta-agonists in adults with acute asthma also indicates a higher incidence of adverse effects associated with IV aminophylline.

Authors' conclusions: In the included RCTs there was no consistent evidence favouring either IV beta(2)-agonists or IV aminophylline for patients with acute asthma. The opportunity to draw clear conclusions is limited by the heterogeneity of outcomes evaluated and the small sample sizes in the included studies. It is recommended that these data should be viewed carefully alongside the conclusions from separate Cochrane reviews comparing IV beta(2)-agonists plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone and IV aminophylline plus inhaled beta(2)-agonists versus inhaled beta(2)-agonists alone.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review
  • Systematic Review

MeSH terms

  • Acute Disease
  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Adrenergic beta-2 Receptor Agonists / adverse effects
  • Adult
  • Aminophylline / administration & dosage*
  • Aminophylline / adverse effects
  • Anti-Asthmatic Agents / administration & dosage*
  • Anti-Asthmatic Agents / adverse effects
  • Asthma / drug therapy*
  • Bronchodilator Agents / administration & dosage*
  • Bronchodilator Agents / adverse effects
  • Child
  • Emergencies
  • Heart Rate / drug effects
  • Humans
  • Injections, Intravenous
  • Length of Stay
  • Randomized Controlled Trials as Topic


  • Adrenergic beta-2 Receptor Agonists
  • Anti-Asthmatic Agents
  • Bronchodilator Agents
  • Aminophylline